IP Library › Granted Patent US 12,433,854
Granted Patent B2
US 12,433,854 · App. 18/231,035 · Granted Oct 7, 2025

Methods and compositions for preventing or treating calciphylaxis

Inventors: James A. Tumlin (Lawrenceville, GA); Paul L. Darke (Hingham, MA); John M. Rudey (New York, NY)
Assignee: Epizon Pharma, Inc.
A61K31/122A61K31/047A61K31/22A61K31/366A61K31/40A61K31/405A61K31/47A61K31/505A61P3/14A61P13/12
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Quick Facts
Patent No.
US 12,433,854
App. No.
18/231,035
Granted
Oct 7, 2025
Kind
B2
Abstract

The invention provides methods and compositions for preventing or treating (e.g., slowing the progression of, arresting, and/or reversing) calciphylaxis in a subject in need thereof and, more particularly, the invention relates to methods of using menaquinone-7 (MK-7) and/or menaquinol-7 (MKH2-7) for preventing or treating calciphylaxis in a subject with one or more of the following: diabetes, chronic kidney disease, end stage renal failure, and COPD or a subject undergoing hemodialysis and/or receiving anticoagulant therapy and/or statin therapy.

Claims (47)

1. A method of treating calciphylaxis in a human subject in need thereof, the method comprising administering to the human subject a composition comprising menaquinol-7 (MKH2-7) thereby to treat calciphylaxis in the subject,

whereupon the administration of the MKH2-7 to the subject:

(i) decreases a plasma level of Highly Sensitive C Reactive Protein (hs-CRP) relative to the plasma level of hs-CRP prior to administration; or

(ii) increases a plasma level of osteoprotegerin relative to the plasma level of osteoprotegerin prior to administration.

2. The method of claim 1 , wherein the subject has distal calciphylaxis and/or central calciphylaxis.

3. The method of claim 1 , wherein the subject has diabetes, chronic kidney disease, or end stage renal disease.

4. The method of claim 3 , wherein the subject has stage 3, 4, or 5 chronic kidney disease.

5. The method of claim 1 , wherein the subject is undergoing hemodialysis.

6. The method of claim 1 , wherein the subject is receiving non-warfarin-based anti-coagulant therapy.

7. The method of claim 6 , wherein the anti-coagulant therapy is oral anti-coagulation therapy.

8. The method of claim 6 , wherein the anti-coagulation therapy comprises an inhibitor of Factor Xa activity or Factor IIa activity.

9. The method of claim 1 , wherein the subject has chronic obstructive pulmonary disease (COPD).

10. The method of claim 1 , wherein the subject has a calciphylaxis-related dermal lesion.

11. The method of claim 10 , wherein administration of the composition reduces the size of the dermal lesion.

12. The method of claim 1 , whereupon administration of the MKH2-7 to the subject increases the subject's serum T50 value relative to the subject's serum T50 value prior to administration of the MKH2-7.

13. The method of claim 1 , wherein administration of the MKH2-7:

(a) increases a ratio of a carboxylated to a non-carboxylated of a Vitamin K-dependent protein; or

(b) decreases an amount of a non-carboxylated Vitamin K-dependent protein in plasma of the subject relative to the ratio or amount present prior to administration of the MKH2-7.

14. The method of claim 13 , wherein the Vitamin K-dependent protein is selected from Matrix Gla Protein, Growth Arrest Specific Gene 6 (Gas-6) protein, PIVKA-II protein, osteocalcin, activated Protein C, or activated Protein S.

15. The method of claim 1 , wherein upon administration of the MKH2-7 to the subject increases a plasma level of osteoprotegerin relative to the plasma level of osteoprotegerin prior to administration of the MKH2-7.

16. The method of claim 1 , wherein upon administration of the MKH2-7 to the subject decreases a plasma level of D-Dimer relative to the plasma level of D-Dimer prior to administration of the MKH2-7.

17. The method of claim 1 , wherein from about 10 mg to about 50 mg of MKH2-7 is administered to the subject per day.

18. The method of claim 1 , wherein 10, 25, 50, 75, or 100 mg of MKH2-7 is administered to the subject per day.

19. The method of claim 1 , wherein the composition is administered to the subject for at least 2 weeks.

20. The method of claim 1 , wherein the composition is administered daily.

21. The method of claim 1 , whereupon the administration of the MKH2-7 to the subject decreases a plasma level of Highly Sensitive C Reactive Protein (hs-CRP) relative to the plasma level of hs-CRP prior to administration.

22. A method of increasing vascular compliance in a subject in need thereof, the method comprising administering to the subject an effective amount of menaquinone-7 (MK-7) and/or menaquinol-7 (MKH2-7), the method comprising administering to the human subject a composition comprising MK-7 and/or MKH2-7 thereby to increase vascular compliance in the subject,

whereupon the administration of the MK-7 and/or MKH2-7 to the subject:

(i) increases a plasma level of Fetuin A relative to the plasma level of Fetuin A prior to administration;

(ii) decreases a plasma level of Highly Sensitive C Reactive Protein (hs-CRP) relative to the plasma level of hs-CRP prior to administration; or

(ii) increases a plasma level of osteoprotegerin relative to the plasma level of osteoprotegerin prior to administration.

23. The method of claim 22 , whereupon the administration of the MK-7 and/or MKH2-7 to the subject increases a plasma level of Fetuin A relative to the plasma level of Fetuin A prior to administration.

24. The method of claim 22 , whereupon the administration of the MK-7 and/or MKH2-7 to the subject decreases a plasma level of Highly Sensitive C Reactive Protein (hs-CRP) relative to the plasma level of hs-CRP prior to administration.

25. The method of claim 22 , wherein upon administration of the MK-7 and/or MKH2-7 to the subject increases a plasma level of osteoprotegerin relative to the plasma level of osteoprotegerin prior to administration of the MK-7 and/or MKH2-7.

26. The method of claim 22 , whereupon administration of the MK-7 and/or MKH2-7 to the subject increases the subject's serum T50 value relative to the subject's serum T50 value prior to administration of the MK-7 and/or MKH2-7.

27. The method of claim 22 , wherein administration of the MK-7 and/or MKH2-7:

(a) increases a ratio of a carboxylated to a non-carboxylated of a Vitamin K-dependent protein; or

(b) decreases an amount of a non-carboxylated Vitamin K-dependent protein in plasma of the subject relative to the ratio or amount present prior to administration of the MK-7 and/or MKH2-7.

28. The method of claim 27 , wherein the Vitamin K-dependent protein is selected from Matrix Gla Protein, Growth Arrest Specific Gene 6 (Gas-6) protein, PIVKA-II protein, osteocalcin, activated Protein C, or activated Protein S.

29. The method of claim 22 , wherein upon administration of the MKH2-7 to the subject decreases a plasma level of D-Dimer relative to the plasma level of D-Dimer prior to administration of the MK-7 and/or MKH2-7.

30. The method of claim 22 , wherein from about 10 mg to about 50 mg of MK-7 and/or MKH2-7 is administered to the subject per day.

31. The method of claim 22 , wherein 10, 25, 50, 75, or 100 mg of MK-7 and/or MKH2-7 is administered to the subject per day.

32. The method of claim 22 , wherein the composition is administered to the subject for at least 2 weeks.

33. The method of claim 22 , wherein the composition is administered daily.

34. The method of claim 22 , wherein the vascular compliance is aortic compliance.

35. The method of claim 22 , wherein the administration of the MK-7 and/or MKH2-7 increases vascular compliance by at least 5% relative to vascular compliance prior to treatment.

36. The method of claim 22 , wherein the increased vascular compliance is measured using pulse wave velocity (PWN).

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 29, 2025
From: TUMLIN, JAMES A.; DARKE, PAUL L.; RUDEY, JOHN M.
To: EPIZON PHARMA, INC.
Reel/Frame 072772/0627 →
Continuity (5)
Continuation 17349663 · Jun 16, 2021
Continuation 16902705 · Jun 16, 2020
Division 16435230 · Jun 7, 2019
Provisional Application 62682794 · Jun 8, 2018
Related Publication 20240041794A1 · Feb 8, 2024
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